The mixing of pharmaceutical compositions is a crucial step in processing an active drug into a form for administration to a recipient. Pharmaceutical compositions usually consist of five (5) or more separate components, including the active drug, which must be mixed into a homogeneous mixture. It is critical to determine the concentration of the active drug in a pharmaceutical mixture. It is also advantageous to determine the concentration of the other non-active components within the final homogeneous mixture. The assurance that the pharmaceutical composition is homogeneous is necessary in order to ensure the appropriate dosage of the active drug is delivered to a recipient.
The concentration of the non-active components in a pharmaceutical mixture is also important because it determines the physical properties of the mixture. For example, the non-active components of pharmaceutical compositions are known as excipients. An example of an excipient is a disintegrant. Disintegrants determine the rate of dissolution of a tablet in a recipient's stomach. Therefore, if the disintegrant is not homogeneously distributed in the pharmaceutical mixture, then the resulting tablets may not dissolve at a uniform rate. This could give rise to quality, dosing and bioavailability problems.
Typically, homogeneity of a pharmaceutical composition referred to the distribution of the active drug in the pharmaceutical composition. Potency of a pharmaceutical composition referred to the amount of the active component in a pharmaceutical composition. Traditionally, the determination of the potency and homogeneity of a pharmaceutical mixture has been time consuming. In addition, traditional methods measure the potency and homogeneity of only the active component in a pharmaceutical composition and gives no information concerning the homogeneity of the non-active components.
The traditional methods typically involve using a conventional blender such as a core blender, a ribbon blender, a "V"-blender or the like, to mix the components of a pharmaceutical composition. When the mixture is thought to be finished, the blender is stopped and usually nine or more samples of the mixture are removed from various locations in the conventional blender. The blender remains shut down while the samples are taken to a laboratory and analyzed for potency. The samples are typically analyzed using High Performance Liquid Chromatography (HPLC). The HPLC analysis determines the concentration of only the active component in each of the samples. The measurements determine whether the active component is uniformly dispersed or homogeneous in the mixture and present at an appropriate concentration level. This information reflects the potency of the mixture and if the potency of each of the samples is the same, then the mixture is considered to be homogeneous. HPLC analysis does not establish the concentration of the non-active components of the mixture. Homogeneity of all the components of a pharmaceutical mixture is important because the dispersion of certain components will ultimately affect the physical properties of the final form of the pharmaceutical composition, as discussed hereinabove. The traditional analysis can take from 24 to 48 hours to complete.
Another time consuming aspect of the traditional method is the hit or miss approach to determine when the mixture is homogeneous. Typically, the blender is run for a predetermined amount of time. The blender is stopped and the samples are taken to be tested. If the mixture is not homogeneous then the blender is run again and the testing procedure is repeated. Further, the mixture may reach homogeneity at a time-point before the predetermined set time for blending. In the first case more testing is carried out than is required, and in the second case valuable time is wasted in blending beyond the end-point. It is also possible that over blending can cause segregation of the components. Therefore, the time that is wasted in both cases and the possible risk of segregation due to over blending can be avoided by an apparatus which could detect on-line the potency and homogeneity of the pharmaceutical mixture. The term on-line means that the blender does not have to be turned off in order to take the measurements to determine homogeneity and potency.
For the foregoing reasons, there has been a long felt need in the art for an apparatus which can blend the components of a pharmaceutical mixture and detect on-line the potency and homogeneity of all the components of a pharmaceutical mixture. There is currently no apparatus in the art which can blend a pharmaceutical composition and detect on-line the homogeneity and potency of a pharmaceutical mixture.